This revised proposal requests 4-year support for a BRTP Biomedical Computing Resource that emphasizes quantitative biomedical imaging. Goals are to 1) develop new computing technologies important to health- related research, 2) collaborate with biomedical scientists to solve problems requiring advanced computing techniques, 3) make Resource capabilities accessible to investigators, 4) train scientists in biomedical computing, and 5) develop and field useful biomedical- computing systems, locally and nationally. Technological R&D spans theoretical developments through implementation and exportation of systems. Theoretical developments include modeling of biological phenomena and of transduction for data acquisition. The development of computing methodologies includes 1) modeling plus algorithm development for abstracting image information from measurement data, 2) the application of high-performance processors, and 3) the development of systems that can be expeditiously transported and integrated into the environments of our collaborators and the broader scientific community. Specific areas of core research include 1) algorithms for advancing positron-emission tomography by improving attenuation corrections, applying information from other sources to image estimations, and extending current methods to 3-dimensional data, 2) modeling and image-estimation methods for improving both scanning and computational optical-sectioning microscopy, and 3) new approaches to global shape modeling and image representation to accommodate multiple levels of variability in multi-dimensional biomedical images. Technological development includes 1) exploitation of both SIMD and MIMD parallel-processing methods for achieving useful performance of computationally challenging algorithms, and 2) high-speed communication systems for distributing Resource capabilities to dispersed sites for both technological and biomedical research. An integrated environment for quantitative-imaging research is maintained. Collaborative research includes 9 intramural (Washington University) and 9 extramural projects in: functional brain mapping, cognitive neuroscience, myocardial and tumor imaging, statistical methods in image analysis, cerebral blood flow via MRI, multicellular morphogenesis, embryonic actin-binding proteins, postsynaptic-receptor plasticity, high- resolution fluorescence microscopy, anti-HIV oligonucleotides, pattern- theoretic methods, deformable topologic templates, radiation-treatment planning, ocular-fundus imaging, ATM-based networking, genetic-linkage analysis, cellular biochemistry in cardiac ischemia, scatter corrections for PET, DNA mapping, and electron-microscopic autoradiograph analysis. Four Resource technologies provide user service for 10 intramural and 5 extramural research projects.